Yang, Gabsik;Lee, Seon Joo;Kang, Han Chang;Cho, Yong-Yeon;Lee, Hye Suk;Zouboulis, Christos C.;Han, Sin-Hee;Ma, Kyung-Ho;Jang, Jae-Ki;Lee, Joo Young
Biomolecules & Therapeutics
/
v.28
no.5
/
pp.437-442
/
2020
Activation of the NLRP3 inflammasome is critical for host defense as well as the progression of inflammatory diseases through the production of the proinflammatory cytokine IL-1β, which is cleaved by active caspase-1. It has been reported that overactivation of the NLRP3 inflammasome contributes to the development and pathology of acne vulgaris. Therefore, inhibiting activation of the NLRP3 inflammasome may provide a new therapeutic strategy for acne vulgaris. In this study, we investigated whether auranofin, an anti-rheumatoid arthritis agent, inhibited NLRP3 inflammasome activation, thereby effectively treating acne vulgaris. Auranofin suppressed NLRP3 inflammasome activation induced by Propionibacterium acnes, reducing the production of IL-1β in primary mouse macrophages and human sebocytes. In a P. acnes-induced acne mouse model, injection of P. acnes into the ears of mice induced acne symptoms such as redness, swelling, and neutrophil infiltration. Topical application of auranofin (0.5 or 1%) to mouse ears significantly reduced the inflammatory symptoms of acne vulgaris induced by P. acnes injection. Topical application of auranofin led to the downregulation of the NLRP3 inflammasome activated by P. acnes in mouse ear skin. These results show that auranofin inhibits the NLRP3 inflammasome, the activation of which is associated with acne symptoms. The results further suggest that topical application of auranofin could be a new therapeutic strategy for treating acne vulgaris by targeting the NLRP3 inflammasome.
Kim, Sook-Hee;Kim, Jin-Sook;Jin, Mi-Rim;Kim, Ha-Won;Choi, Eung-Chil;Kim, Byong-Kak
Korean Journal of Pharmacognosy
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v.24
no.4
/
pp.267-281
/
1993
To find antitumor components from higher fungi, the mycelia of Collybia confluens (Pers. ex Fr.) Kummer were cultured in artificial media. For efficient production of the mycelia, the influences of various modifications of culture conditions were examined. A water-soluble protein-bound polysaccharide fraction, Fr. A, was obtained from the mycelia by hot water extraction. When Fr. A was purified and fractionated by DEAE-cellulose and Sepbadex G-200 gel filtration chromatographies into four fractions which were designated B, C, C-I and C-II. The tumor inhibition ratios of these fractions ranged from 46% to 75% against the solid forms of sarcoma 180 in ICR mice at doses of 20 and 50 mg/kg/day when given intraperitoneally. Especially, Fr. C which was named Collyban(CB) exhibited a marked life-prolonging effect of the mice against ascitic forms of sarcoma 180 at a dose of 50 mg via i.p. administration. To extend spectra of the antitumor activities and eliminate the effects of allograft rejection, the characterization of antitumor effects of CB was performed in syngeneic host-tumor systems. It did not show any antitumor activity against L1210 murine leukemia in $CD_2Fl$ mice but prolonged their life span against ascitic forms of $MM_{46}$ carcinoma in $C_3H/He$ mice. Also it exhibited antitumor activity against human cervical cancer HeLa cells that were xenografted into nude mice having BALB/c genetic backgrounds by the i.p. injection at a dose of 100 mg/kg/day. In order to characterize the antitumor components, CB was examined by chemical analysis. It was acidic protein-bound polysaccharides composed of 31% polysaccharide, 27% protein and 3% hexosamine. CB was fractionated into two fractions, Fr. C-I(M.W.: 500 Kd) and Fr. C-II(M.W.:30 and 8 Kd) by Sephadex G-200 gel filtration chromatography.
We compared the transcriptome in response to propanol stress in wild-type and propanol-resistant mutant Escherichia coli using the DNA microarray technique. The correlation value of RNA expression between the propanol-treated wild type and the untreated-one was about 0.949, and 50 genes were differentially expressed by more than twofold in both samples. The correlation value of RNA expression between the propanol-treated mutant and the untreated one was about 0.951, and 71 genes in two samples showed differential expression patterns. However, the values between the wild type and mutant, regardless of propanol addition, were 0.974-0.992 and only 1-2 genes were differentially expressed in the two strains. The representative characteristics among differentially expressed genes in W3110 or P19 treated with propanol compared to untreated samples were up-regulation of hest shock response genes and down-regulation of genes relating to ribosome biosynthesis. In addition, many genes were regulated by transcription regulation factors such as ArcA, CRP, FNR, H-NS, GatR, or PurR and overexpressed by sigma factor RpoH. We confirmed that RpoH mediated an important host defense function in propanol stress in E. coli W3110 and P19 by comparison of cell growth rate among the wild type, rpoH disruptant mutant, and rpoH-complemented strain.
The genus Mycobacterium includes crucial animal and human pathogens such as Mycobacterium tuberculosis, Mycobacterium leprae, and Mycobacterium bovis. Although it is important to understand the genetic basis for their virulence and persistence in host, genetic analysis in mycobacteria was hampered by a lack of sufficient genetic tools. Therefore, many functional vectors as molecular genetic tools have been designed for understanding mycobacterial biology, and the application of these tools to mycobacteria has accelerated the study of mechanisms involved in virulence and gene expression. To overcome the pre-existing problems in genetic manipulation of mycobacteria, this paper reports new vector systems as effective genetic tools in Mycobacterium smegmatis. Three vectors were developed; pKOTs is a suicide vector for mutagenesis containing a temperature-sensitive replication origin (TSRO) and the sacB gene encoding levansucrase as a counterselectable marker. pMV306lacZ is an integrative lacZ transcriptional fusion vector that can be inserted into chromosomal DNA by site-specific recombination. pTnMod-OKmTs is a minitransposon vector harboring the TSRO that can be used in random mutagenesis. It was demonstrated in this study that these vectors effectively worked in M. smegmatis. The vector systems reported here are expected to successfully applicable to future research of mycobacterial molecular genetics.
T cells induce immune responses and thereby eliminate infected micro-organisms when peptides from the microbial proteins are bound to HLAs in the host cell surfaces, It is known that the more stable the binding of peptide to HLA is, the stronger the T cell response gets to remove more effectively the source of infection. Accordingly, if peptides (HLA binder) which can be bound stably to a certain HLA are found, those peptieds are utilized to the development of peptide vaccine to prevent infectious diseases or even to cancer. However, HLA is highly polymorphic so that HLA has a large number of alleles with some frequencies even in one population. Therefore, it is very inefficient to find the peptides stably bound to a number of HLAs by testing random possible peptides for all the various alleles frequent in the population. In order to solve this problem, computational methods have recently been developed to predict peptides which are stably bound to a certain HLA. These methods could markedly decrease the number of candidate peptides to be examined by biological experiments. Accordingly, this paper not only introduces a method of machine learning to predict peptides binding to an HLA, but also suggests a new prediction model so called 'knowledge-based genetic algorithm' that has never been tried for HLA binding peptide prediction. Although based on genetic algorithm (GA). it showed more enhanced performance than GA by incorporating expert knowledge in the process of the algorithm. Furthermore, it could extract rules predicting the binding peptide of the HLA alleles common in Koreans.
Jo Ji-Yun;Jeong Jin-Yong;Kang Ho Young;Kim Gun-Do;Byeon Jeong-Sik;Myung Seung-Jae;Jung Hwoon-Yong;Yang Suk-Kyun;Hong Weon-Seon;Kim Jin-Ho;Lee Gin Hyug
Journal of Life Science
/
v.15
no.6
s.73
/
pp.904-908
/
2005
Recently the pathological actions of CagA of Helicobacter pylori (H. pylori) on gastric epithelial cells have been reported. CagA is directly injected into the host cytoplasm and undergoes tyrosine phosphorylation in the cells. In addition, translocated CagA forms a physical complex with SHP-2. There are two major CagA subtypes according to the amino acid sequence in the 3'region of CagA; i) the East Asian type (A-B-D of EPIYA motifs) and ii) the Western type (A-B-C of EPIYA motifs). Repeated EPIYA motifs in the 3'region of CagA are involved in the interaction with SHP-2. The East Asian type conferred stronger SHP-2 binding activity than the Westrrn type of CagA. Here we analyzed the amino acid sequences of the SHP-2 binding site of cagA gene in H. pyzori, and investigated whether there is my relationship between the diversities of cagA and the disease out-come in Korea. Most of Korean H. pylori strains showed A-B-D motifs(the East Asian type), and only one strain showed A-B-B-D motifs. In Korea, the incidence of atrophic gastritis and gastric cancer is significantly high compared with Western countries. The high frequency of the East Asian type CagA among Korean H. pylori strains would be involved in increasing the risk of gastric cancer in Korean populations.
Objective: To analyze the treatment-related parameters after the radiotherapy of T1N0 squamous cell carcinoma of the glottic larynx. Materials and Methods: Between October 1989 and August 2000, 54 patients with histologically proven T1N0 squamous cell carcinoma of the glottic larynx who received definitive radiation therapy in Department of Radiation Oncology, Asan Medical Center were analyzed. They were all males with age ranged from 31 to 80 years (median 61 years). 1997 AJCC stages were 31 T1a, 23 T1b. Patients were treated with 4-MV X-rays with a parallel-opposed two-field technique. Ten patients received 66.0-68.4Gy at 1.2Gy per fraction twice daily, 21 patients received 64.8-66.6Gy at 1.8Gy per fraction once daily, and 23 patients received 66.0Gy at 2.0Gy per fraction once daily. Follow-up period was 16-119 months (median 56 months). Results: 5-year overall survival and local control rates for patients with T1 lesions were 87.0% and 88.5%, respectively. 5-year local control with larynx preservation rate was 90.5%. Host and tumor-related prognostic factors including age, stage, anterior commissure involvement and tumor bulk proved not to be significant. Only shorter overall treatment time among treatment-related factors had correlation with imporved local control. Conclusion: Comparable high local control rate with organ preservation was achieved with primary radiation therapy and salvage surgery. Shortening of overall treatment time is related to improved local control rate. To determine the optimal fractionation scheme, randomized trial is mandatory.
Kim, Soo-Yong;Choi, Myung-Sik;Chang, Woo-Hyun;Cha, Chang-Yong
The Journal of the Korean Society for Microbiology
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v.22
no.3
/
pp.233-240
/
1987
The amniotic fluid provides a medium in which the fetus can readily move, cushions him against possible injury and helps him maintain an even temperature. Besides above mentioned functions, investigators reported that human amniotic fluid contains host-resistance factors which prevent bacteria from producing infectious disease and this activity shows difference among human racial groups or bacterial genera, species and strains. 40 amniotic fluid specimens from Korean women in their second and third trimesters of pregnancy were examined for inhibiting the growth of Escherichia coli. And various factors which might affect bacterial growth inhibiting activity such as pH, initial inoculum size, concentration of amniotic fluid, and heat resistance, were also tested using a strongly inhibitory amniotic fluid specimen. Finally plate diffusion tests were carried out using other strongly inhibitory amniotic fluid. The following results were obtained: 1. Of the 40 fluid samples examined, 18 specimens(45%) had inhibitory activity and samples from women in their second trimester of pregnanancy showed non-inhibitory activity(2 specimens). 2. The pH of the fluids varied between 7.43 and 8.33. There was no correlation between pH and inhibitory activity. 3. No. 19 amniotic fluid showed bacteriostatic activity after 24 hours incubation when an inoculum of $10^2$ organisms per milliliter was used, but non-inhibitory with an inoculum of $10^3$ and $10^4$ bacteria per milliliter. 4. The content of amniotic fluid in culture media influenced E. coli growth. At 90 percent, E. coli was inhibited growth but at 10 percent and 50 percent. 5. Inhibitory activity of No. 19 amniotic fluid was retained after heating to $50^{\circ}C$ for 30 minutes or 100^{\circ}C$ for 30 minutes. 6. Plate diffusion tests with No. 27 amniotic fluid showed that 0.7ml amniotic fluid gave clear zone of growth inhibition around the central well but 0.2ml and 0.1ml amniotic fluids were not.
To understand host-defence mechanism of clam(Ruditapes philippinarum) hemocyte against foreign materials, classification and their seasonal change in the number were performed. clams collected from a farm in Julpo Bay, Gochang, Chollabuk-Do were used in this experiment. Lots of hemocytes were found between the muscle fibers and connetive tissue of posterior adductor muscle. Hemocytes of R. philippinarum were classified into granulocytes and agranulocytes. Granulocytes were composed of three types, basophilic granulocyte, acidophilic granulocyte and fibrocyte in accordance with the staining affinities of their cytoplasmic granules. Fibrocyte has filopodia and vesicle in endoplasm and bigger than other granulocytes in size. Agranulocytes were less in the number and smaller in the size compared to those of granulocytes. Hyalinocytes had no granule in their cytoplasm. The nucleus located in the center of the cell was oval or spherical shaped. In electron microscopic observation, granulocytes and hyalinocytes contained electron-dense vesicles and some small lucid vesicles in their cytoplasm, respectively. Granulocytes phagocytosed more zymosan particles than hyalinocytes. Acidophilic granulocytes showed higher phagocytic ratio than basophilic granulocytes. Total hemocyte numbers showed the highest at April to August and the lowest at October to December. In the composition of each hemocyte, basophilic granulocytes were always more than acidophilic granulocytes and hyalinocytes.
Scuticociliates Miamiensis avidus (syn. Philasterides dicentrarchi) causes high mortality and bad growth in olive flounder Paralichthys olivaceus. Temperature is an important factor not only for growth of pathogens but also for host immune system in poikilothermal animal. In this study, temperature affecting ciliate growth and pathogenicity against olive flounder were examined. Doubling time for the ciliate growth was 61.82 hours at $5{^{\circ}C}$, 26.32 hours at $10{^{\circ}C}$, 21.14 hours at $15{^{\circ}C}$, 16.86 hours $20{^{\circ}C}$ and 16.21 hours at $25{^{\circ}C}$. Maximum ciliate numbers were similar at $10-20{^{\circ}C}$ at the range of $1.54-1.75{\times}10^{5}$/ ml. Duplicated intraperitoneal injections were conducted with the ciliates by the concentrations of $1{\times}10^{2}$, $1{\times}10^{6}$, $1{\times}10^{4}$and $1{\times}10^{5}$/ fish (average 8.34 cm, 4.33 g) then kept at $10{^{\circ}C}$, $15{^{\circ}C}$ and $20{^{\circ}C}$. Cumulative mortality was low at $10{^{\circ}C}$ and the mortality was increasing at higher water temperatures. In addition, cumulative mortality was higher at higher dose of infections. In conclusion, Scuticocilite M. avidus grew well at higher temperature (at $5{^{\circ}C}$, $10{^{\circ}C}$, $15{^{\circ}C}$ and $25{^{\circ}C}$) in vitro, and olive flounder mortality due to M. avidus was highly water temperature and dose dependent. The results of this study suggest that water temperature control may one of the essential factor to reduce mortality due to M. avidus infection.
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